[Construction of natural population cohort on telephone follow-up management quality control system and discussion regarding critical issues by REDCap system].

With completing a baseline survey of a large natural population cohort, conducting regular follow-up has become a key factor in further improving the quality of cohort construction and ensuring its sustainable development. Typical cohort follow-up methods include repeat surveys, routine monitoring, and community-oriented surveillance. However, in practical applications, there are often issues such as high costs, difficulty, and high error rates. Telephone follow-up is an important supplementary method to the methods mentioned above, as it has the characteristics of low cost, fast response, and high quality. However, the with difficult organization, quality control is challenging, response rates are low, and management levels vary widely, which limits its widespread use in large-scale population cohort studies. Given the above problems, this study draws on customer relationship management based on the actual needs of the China Northwest Cohort follow-up. It relies on the REDCap electronic data collection platform to build a telephone follow-up management and quality control system. Targeted solutions are provided for key issues in telephone follow-up implementation, including organizational structure, project management, data collection, and process quality control, to improve the quality control level of telephone follow-up comprehensively and thereby enhance the quality and efficiency of follow-up. We hope to provide standardized follow-up programs and efficient quality control tools for newly established and existing cohort studies.

[Relationship between Chinese dietary guidelines compliance index for pregnant women and congenital heart disease in offspring].

Objective: To study the relationship between the Chinese dietary guidelines compliance index for pregnant women (CDGCI_PW) and congenital heart disease (CHD) in offspring. Methods: In a hospital-based case-control study conducted in Xi'an, Shaanxi province, semi-quantitative food frequency questionnaires were used to investigate the diets of pregnant women throughout pregnancy. The modified CDGCI_PW score was used to evaluate dietary quality during pregnancy, logistic regression was applied to analyze the relationship between CDGCI_PW score and offspring CHD, and the ROC curve was adopted to construct the prediction model of CDGCI_PW for offspring CHD. Results: A total of 1 422 subjects were enrolled, including 474 in the case group and 948 in the control group. The CDGCI_PW score in the case group M (Q1, Q3) was 46.0 (26.0, 65.0) lower than that in the control group, which was 60.0 (40.0, 77.0). The difference between the two groups was significant (P<0.001). Compared with those in the Q1 of CDGCI_PW, the offspring in the Q2, Q3, and Q4 of CDGCI_PW had a lower risk of total CHD (OR=0.60, 95%CI: 0.43-0.83; OR=0.64, 95%CI: 0.45-0.89; OR=0.29, 95%CI: 0.19-0.44), with the trend test P<0.001. The risk of total CHD was reduced by 17% (OR=0.83, 95%CI: 0.79-0.88) when 10 points increased the CDGCI_PW score. The area under curve predicted by constructing the ROC curve was 0.793 (95%CI: 0.768-0.818), and at the maximum of the Youden index, the sensitivity was 0.740, and the specificity was 0.725. Conclusion: This study suggests that improving dietary quality during pregnancy may reduce the risk of CHD in offspring.

[Application of isotemporal substitution model in epidemiological research].

Isotemporal substitution model is a powerful tool to explore the real association between physical behavior and health outcomes, which has the potential of the application in large-scale cohort study. This paper systematically introduces the principle of isotemporal substitution model and its implementation method in specific analysis to provide analytical ideas for the epidemiological research related to physical behavior in China. The baseline data of Regional Ethic Cohort Study in Northwest China conducted in Shaanxi province were used to analyze the relationship between physical behavior and cardiovascular disease with single-factor model, partition model and isotemporal substitution model. The advantages and disadvantages of different models were compared, and the advantages of isotemporal substitution model in quantifying physical activity health risk were introduced. Isotemporal substitution model could qualify physical behavior and health outcomes, which has wide application value in epidemiological research.

[The association between calcium supplementation in antenatal childbearing aged women and risk of small for gestational age among neonatal singleton in Shaanxi province].

Objective: This study explored the association between antenatal calcium supplementation in the childbearing aged women and risk of small for gestational age infant (SGA) among singleton in Shaanxi province,China. Methods: Multi-stage random cluster sampling method was employed to collect information about pregnant women, who were pregnant and had definite outcomes, and their infants, from 30 districts (counties) in 2010 to 2013. Information was collected by face-to-face questionnaire survey. Generalized linear mixed models were employed after adjusting covariates. Dependent variable was whether single-birth neonate was SGA, and independent variable was calcium supplementation of childbearing aged women in different pregnant periods. Results: A total of 28 357 childbearing aged women was recruited in this study. The age of these women was (28.08±4.74) years old, of which, 79.28% were rural residents and 60.90% had calcium supplementation intake. There was a number of 12 810 female in singleton neonates. The neonatal birth weight and gestational age were (3.27±0.16) kg and (277.44±8.80) day, respectively. The prevalence of SGA was 11.35% in total, and 10.48% in mothers with maternal calcium supplementation and 12.70% in mothers without maternal calcium supplementation in whole antenatal period. There were statistically significant differences seen in antenatal calcium supplementation within the subgroups of maternal age (whether the mother was an advanced maternal woman), residential area, maternal occupation, maternal parity, maternal education level, and household incomes (P<0.05). After adjusting these covariates, the risk of SGA among childbearing aged women with antenatal calcium supplementation showed 16% decreased risk (OR=0.84, 95%CI: 0.77-0.92). Further analysis of the different antenatal periods showed that calcium supplementation during the second and third trimester had a statistically significant difference in reducing the risk of neonatal SGA (P<0.05). Besides, subgroup analysis showed that there was a statistically significant difference between the perinatal calcium supplementation and the single-born neonates with SGA Significance (P<0.05) in non-advanced women, those who had a low education level and moderate household economic status groups. Conclusion: The risk reduction of SGA among singleton neonates is related to calcium supplementation during antenatal period in Shaanxi province.

[Method of double data entry and quality control by REDCap system].

In medical research, the quality of data is the key to success. Thus, data quality control becomes an important part of ensuring the research's high quality. REDCap system is an emerging data acquisition system in medical research, which is gradually applied in research at home and abroad. It is a hot issue to realize double data entry and data quality control in using the REDCap system, which researchers are concerned about when this system is supposed to apply. This article will systematically introduce how to use the REDCap system for double data entry and quality control from the aspects of research project creation, data collection tool design, double data entry, data checking and exporting.

[Application of electronic data acquisition system REDCap in large natural population-based cohort studies].

Cohort study is one of the basic methods used in epidemiological research. With the development of the etiological analysis of complex diseases such as cardiovascular diseases, large natural population-based cohort study has become a popular topic in medical research. In the process of cohort development, one of the important issues is to ensure the efficiency and safety on data collection. As a database management system, with open source, free clinical research data collection and high quality, REDCap can widely be applied in large population-based cohort studies. This article summarizes the baseline survey and follow-up procedures on cohort studies and introduces a REDCap-system-based solution for data collection and management. Contents on the establishment of data working groups, data collection, cohort follow-up methods and field application are also discussed in this paper, in order to improve the efficiency of data collection and management in cohort study to help the development of cohort study in China.

[WITHDRAWN: Potential false-positive rate among the 'asymptomatic infected individuals' in close contacts of COVID-19 patients].

Editor office's response for Ahead of Print article withdrawn The article "Potential false-positive rate among the 'asymptomatic infected individuals' in close contacts of COVID-19 patients" was under strong discussion after pre-published. Questions from the readers mainly focused on the article's results and conclusions were depended on theoretical deduction, but not the field epidemiology data and further researches were needed to prove the current theory. Based on previous discussions, the article was decided to be offline by the editorial board from the pre-publish lists. Objective: As the prevention and control of COVID-19continues to advance, the active nucleic acid test screening in the close contacts of the patients has been carrying out in many parts of China. However, the false-positive rate of positive results in the screening has not been reported up to now. But to clearify the false-positive rate during screening is important in COVID-19 control and prevention. Methods: Point values and reasonable ranges of the indicators which impact the false-positive rate of positive results were estimated based on the information available to us at present. The false-positive rate of positive results in the active screening was deduced, and univariate and multivariate-probabilistic sensitivity analyses were performed to understand the robustness of the findings. Results: When the infection rate of the close contacts and the sensitivity and specificity of reported results were taken as the point estimates, the positive predictive value of the active screening was only 19.67%, in contrast, the false-positive rate of positive results was 80.33%. The multivariate-probabilistic sensitivity analysis results supported the base-case findings, with a 75% probability for the false-positive rate of positive results over 47%. Conclusions: In the close contacts of COVID-19 patients, nearly half or even more of the 'asymptomatic infected individuals' reported in the active nucleic acid test screening might be false positives.

[Significance and expression of PAX8, PAX2, p53 and RAS in ovary and fallopian tubes to origin of ovarian high grade serous carcinoma].

Objective: To explore the origin of ovarian high grade serous carcinoma (HGSC) through analysing the expression and significance of PAX8, PAX2, p53 and RAS in the ovary and fallopian tube of different types and grades of serous carcinoma. Methods: A total of 44 cases tissue samples of ovarian tumor including 34 malignant ovarian tumor and 10 normal normal tissue (as control group) were collected from the admitted patients in Affiliated Tumor Hospital of Guangxi Medical University from January 2015 to January 2016. Fallopian tube tissues were segmented in accordance with the fimbria, ampulla, isthmus and the corresponding ovarian tissues were by the side. There were 34 cases of patients with ovarian cancer including 29 cases of epithelial ovarian cancer (27 serous carcinoma, 1 mucinous carcinoma,1 endometrioid adenocarcinoma) and 5 non-epithelial ovarian cancer (sex cord-interstitial tumor). Among 27 cases of patients with ovarian serous cancer, there were 23 HGSC and 4 low-grade ovarian serous cancer (LGSC). One hundred fifty-three cases of samples were diagnosed as ovarian serous cancer by Shandong University Affiliated Qilu Hospital from 2005 to 2013 and these samples were made tissue microarray. (1) To analyze the expression and differences of PAX8, PAX2, p53 and RAS in the above tissues and tissue microarray from ovarian and tubal of HGSC and control women by immunohistochemistry methods. (2) To compare the expression levels of PAX8, PAX2, p53 and RAS in ovarian and fallopian tubes of ovarian cancer patients with different pathological types. (3) To analyze the correlations of tubal and ovarian tissue in PAX8, PAX2, p53 and RAS expression of HGSC. (4) To analyze the factors of the prognosis of ovarian serous cancer in tissue microarray by single factor analysis method. Results: (1) PAX8, PAX2, p53 and RAS expression was negative in normal ovarian epithelium of control group, but the expression of PAX8, PAX2, p53 and RAS were strongly positive brown in secrete cells of normal fallopian tube epithelium. (2) p53 and RAS expression of fallopian tube epithelium in the epithelial ovarian cancer group were significantly higher than those in the non-epithelial ovarian cancer groups (P<0.05), but the expression of PAX8 and PAX2 in fallopian tube and the expression of PAX8, PAX2, p53 and RAS in ovarian tissue was not statistically significant in the groups (P>0.05). PAX8, PAX2 and p53 expression of the ovarian in HGSC group were significantly higher than those in LGSC group (P<0.05), while the expression of RAS was lower in the ovarian of the high-grade group (P<0.05), while the expression of PAX8, PAX2, p53 and RAS in fallopian tube was not statistically significant in the groups (P>0.05). (3) There was a significantly positive correlation between fallopian tube and the corresponding ovary of HGSC in PAX8 and PAX2 expression (r=0.422, P=0.045; r=0.693, P=0.000), but not correlation in p53 and RAS expression (r=0.058, P=0.793; r= -0.190, P=0.384). (4) Univariate survival analysis showed that the progression free survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8, PAX2 and RAS (P<0.05), but there were not correlated with age, surgical staging, cell differentiation, lymph node metastasis and preoperative chemotherapy and p53 protein expression (P>0.05). The total survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8 (P<0.05), but there were not correlated with age,surgical staging, cell differentiation, lymph node metastasis and preoperative chemotherapy and the protein expression of PAX2, RAS and p53 (P>0.05). Conclusions: PAX8, PAX2, p53, RAS are of great significance for the study of origin of HGSC. HGSC may be derived from fallopian tube, but further investigation would be necessary to confirm this. PAX8, PAX2, p53, RAS could be expected to be used as predictors of survival prognosis in patients with ovarian serous cancer.

[Study of the relevant factors of behavioral development among 30-month-old infants in rural area of Shaanxi Province].

Objective: To explore the relevant factors of behavioral development among 30-month-old infants in rural area, Shaanxi Province. Methods: The behavioral development among 977 infants aged 30-month-old was evaluated in Changwu and Binxian of Shaanxi province from July 2006 to August 2008. The inclusion criteria included single live birth between January 2004 and February 2006, mother had participated in a community-based intervention study named "Impact of multi-micronutrient supplementation during pregnancy on low birth weight and premature delivery" . Infants who had obvious deformity or other birth defects, infants who could not complete the questionnaire survey, physical examination were excluded from the study. The self-designed questionnaire was used to investigate the information of feeding patterns, disease status, physical development, and immunization status of the infants, and their behavioral development were assessed by Bayley scales of infant development (BSID). General Linear Model was used to adjust the possible confounding factors, and the analysis of variance was performed to explore the effects on the behavioral development among infants aged 30-month-old. Results: Among the infants in the study, the average age was (30.6±0.6) months old, the mean birth weight was (3 199.1±405.9)g. After adjusted the mothers' age of delivery, educational level and occupation of the parents, family ecnomic conditions and the number of children, infants whose mother exposed to toxic chemicals during pregnancy had lower score in activity (-0.179±0.961) and lower score in concentration (-0.177±1.099) compared with infants with unexposed mother (0.058±1.006, P=0.001; 0.057±0.960, P=0.003). Similarly, infants whose mother took drugs during pregnancy had lower score in persistent behaviors (-0.070±1.000) compared with infants whose mother did not(0.085±1.006, P=0.017). Compared with normal birth infants(0.043±0.981, P=0.007; 0.021±0.984, P=0.034), infants less than gestational age and low birth weight had lower score in concentration(-0.198±1.063 and-0.389±1.285, respectively). After adjusted the delivery gestational age of mothers, the months of infants, the mothers' age of delivery, educational level and occupation of the parents, family ecnomic conditions, the number of children, and the main orderlies of infants, the score of activity of infants suffered from diseases in early month age was-0.049±0.992, which was lower than those who did not(0.207±1.011, P=0.001). The infants with Rickets signs had lower score in motor coordination (-0.218±0.896) than normal infants (0.031±1.011, P=0.013). Infants whose mother with adequate micronutrient supplementation in pregnancy had higher score in concentration (0.066±0.966) than those whose mother with insufficient supplementation (-0.062±1.027, P=0.043). Furthermore, infants with fine protein added and minerals and vitamins added had higher score in activity and concentration compared with those insufficient, who scored 0.078±1.013 and 0.496±0.872 (-0.254±0.924, P<0.001; 0.001±0.997, P=0.033), respectively. Conclusion: Micronutrient supplementation during pregnancy and reasonable nutrition added during childhood could affect behavioral development among infants.

[Study on relationship between mother's animal sourced food intake during pregnancy and neonate birth weight].

Objective: To explore the effect of maternal animal sourced food intake during pregnancy on neonate birth weight and provide scientific basis for guiding the reasonable diet intake in pregnant women and increasing neonate birth weight. Methods: Data were derived from a cross-sectional project of"the prevalence and risk factors of birth defects in Shaanxi province" , which were conducted in 30 counties in Shaanxi province from July to November in 2013. A stratified multistage random sampling method was used to select women who were pregnant between January 2010 and December 2013 for a random semi-quantitative food frequency questionnaire survey to collect the data on the frequency and amount of food consumption on animal protein sources and the data of newborns. Children aged 0-1 years and their mothers were selected as the study subjects. The generalized linear model was used to analyze the relationship between the neonate birth weight and maternal animal sourced food intake during pregnancy, and by using neonate birth weight as dependent variable, food intake frequency as independent variable, three adjustment models were established for stratified analysis. Results: Totally 11 459 participants were involved in this study. The average birth weight of newborn was (3 279.9±454.6) g, the average weekly intake of animal sourced foods was4.00 times for egg, 1.50 times for meat, 3.00 times for dairy foods, 0.50 times for fish and 5.00 times for overall animal sourced foods in pregnant women. Without stratification, three models shown that meat and overall animal sourced food intake had effects on neonate birth weight. After adjustment for gestational weeks, maternal age, social and demographic factors and others, meat intake increased by 1 time a week, the increase of neonate birth weight was about 5.26 (95%CI: 1.32-9.20) g, and the overall animal food increased by 1 times a week, the average neonate birth weight increased by 3.24 (95%CI: 1.09-5.39) g. Stratified analysis showed that meat and overall animal sourced food always had more influences on baby girls and those living in rural area. In the region classification, the overall animal sourced food intake had more influences on women living in northern area and Guanzhong area of Shaanxi, and meat intake had greater influence on women living in southern Shaanxi. And the influences were positive, the more animal sourced foods were taken, the greater the birth weight increased. Conclusion: Animal sourced food intake during pregnancy would benefit the increase of neonate birth weight. It suggests that pregnant women should pay more attention to the intake of animal sourced food.

[Factors related to the influence on congenital malformation of body surface in Shaanxi province].

Objective: To investigate the influencing factors on congenital malformation of body surface. Methods: Multi-stage stratified random sampling method was adopted. A questionnaire survey was conducted among the childbearing aged women who experienced more than 28 weeks pregnancy or having definite pregnancy outcomes in Shaanxi, during 2010-2013. Results: Results from the logistic regression model showed that factors as: intrahepatic cholestasis of pregnancy (OR=21.76, 95%CI: 4.46-106.25), histories with abnormal pregnancy or reproduction (OR=11.88, 95%CI: 9.14-15.45), having birth defects in the family (OR=6.15, 95%CI: 2.66-14.23), being twins (OR=5.74, 95% CI: 3.34-9.86), being worker (compared with others, OR=2.47, 95% CI: 1.30-4.68) or farmer (compared with others, OR=1.91, 95%CI: 1.14-3.20), less than 4 times of antenatal care (compared with >7, OR=1.84, 95% CI: 1.28-2.64), occupational exposure to related risks during pregnancy (OR=1.74, 95% CI: 1.26-2.42), mother's hometown was from mid-part of Shaanxi (compared with northern Shaanxi, OR=1.65, 95%CI: 1.20-2.28), mother's native residence was from the rural areas (OR=1.75, 95% CI: 1.13-2.71), drug use (OR=1.64, 95% CI: 1.26-2.13) etc. were risk factors for congenital malformation of body surface. Iron supplement during pregnancy (OR=0.46, 95%CI: 0.21-0.99) appeared as protective factor for congenital malformation of body surface. Conclusion: The following factors seemed to be of risk for congenital malformation of body surface, including: mother's native area was from the middle part of Shaanxi and living in rural area, being worker or farmer, histories of abnormal pregnancy and reproduction, history of birth defects in the family, being twins, with antenatal care less than 4 times, occupational exposure to dangerous materials, drug use, intrahepatic cholestasis during pregnancy etc.

ß-Arrestin2 encourages inflammation-induced epithelial apoptosis through ER stress/PUMA in colitis.

ß-Arrestins (ß-arrs) are regulators and mediators of G protein-coupled receptor signaling, and accumulating evidence suggests that they are functionally involved in inflammation and autoimmune diseases. However, the effect of ß-arrs is unclear in inflammatory bowel disease (IBD), and the role of ß-arr2 is unknown in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study is to investigate whether ß-arr2 encourages inflammation-induced epithelial apoptosis through endoplasmic reticulum (ER) stress/p53-upregulated modulator of apoptosis (PUMA) in colitis. In the present study, the results showed that ß-arr2 was increased in specimens from patients with UC or CD. Furthermore, a ß-arr2 deficiency significantly repressed intestinal inflammation, ameliorated colitis, and alleviated mucosal apoptosis in mice. In addition, the targeted deletion of ß-arr2 depressed ER stress, inhibited PUMA, and downregulated PUMA-mediated mitochondrial apoptotic signaling in colitis. ß-Arr2, an important modulator of G protein-coupled receptor function, binds eIF2α to activate ER stress signaling. Furthermore, the knockdown of PUMA dramatically prevented ß-arr2-induced apoptosis via alleviating ER stress in vitro. The results suggest that ß-arr2 encourages inflammation-induced epithelial apoptosis through ER stress/PUMA in colitis and that ß-arr2 is a potential therapeutic target for colitis.

Cytomegalovirus infection accelerates the process of chronic rejection in rat liver transplantation.

OBJECTIVE: Analysis of the pathogenesis of cytomegalovirus (CMV) infection for rat chronic liver rejection. METHODS: Based on animal models that we previously developed, we divided control and a CMV infection group to analyze survival, histopathology and rejection activity. The level and mRNA expression of transforming growth factor-ß1, platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) were measured in peripheral blood serum and liver tissue. RESULTS: Obliterative arteriopathy and fibrosis was significantly greater in the CMV infection versus the control group (P < .05). PDGF mRNA expression in rat liver and in peripheral blood were significantly higher in the CMV infection versus the control group (P < .05). bFGF mRNA expression in the CMV infection group was also significantly higher than among the controls (P < .05). CONCLUSIONS: CMV infection aggravated foam cell obliterative arteriopathy and liver fibrosis in chronic liver rejection, processes that accelerate the immune response, which may correlate with early high PDGF and bFGF expression.